Neurogranin as cerebrospinal fluid biomarker for Alzheimer disease: An assay comparison study

Eline A.J. Willemse, Ann De Vos, Elizabeth M. Herries, Ulf Andreasson, Sebastiaan Engelborghs, Wiesje M. Van Der Flier, Philip Scheltens, Dan Crimmins, Jack H. Ladenson, Eugeen Vanmechelen, Henrik Zetterberg, Anne M. Fagan, Kaj Blennow, Maria Bjerke, Charlotte E. Teunissen

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

BACKGROUND: Neurogranin in cerebrospinal fluid (CSF) correlates with cognitive decline and is a potential novel biomarker for Alzheimer disease (AD) dementia. We investigated the analytical and diagnostic performance of 3 commonly used neurogranin assays in the same cohort of patients to improve the interpretability of CSF neurogranin test results. METHODS: The neurogranin Erenna® assay from Washington University, St. Louis, MO (WashU); ELISA from ADx Neurosciences; and ELISA from Gothenburg University, Mölndal, Sweden (UGot), were compared using silver staining and Western blot after gel electrophoresis. Clinical performance of the 3 assays was compared in samples from individuals diagnosed with subjective cognitive decline (n 22), and in patients with AD (n 22), frontotemporal dementia (n 22), dementia with Lewy bodies (n 22), or vascular dementia (n 20), adjusted for sex and age. RESULTS: The assays detected different epitopes of neurogranin: the WashU assay detected the N-terminal part of neurogranin (S10-D23) and a C-terminal part (G49-G60), the ADx assay detected C-terminal neurogranin truncated at P75, and the UGot assay detected the C-terminal neurogranin with intact ending (D78). Spearman was 0.95 between ADx and WashU, 0.87 between UGot and WashU, and 0.81 between UGot and ADx. ANCOVA (analysis of covariance) showed group differences for ranked neurogranin concentrations in each assay (all P 0.05), with specific increases in AD. CONCLUSIONS: Although the 3 assays target different epitopes on neurogranin and have different calibrators, the high correlations and the similar group differences suggest that the different forms of neurogranin in CSF carry similar diagnostic information, at least in the context of neurodegenerative diseases.

Original languageEnglish
Pages (from-to)927-937
Number of pages11
JournalClinical Chemistry
Volume64
Issue number6
DOIs
Publication statusPublished - 1 Jun 2018

Cite this

Willemse, Eline A.J. ; De Vos, Ann ; Herries, Elizabeth M. ; Andreasson, Ulf ; Engelborghs, Sebastiaan ; Van Der Flier, Wiesje M. ; Scheltens, Philip ; Crimmins, Dan ; Ladenson, Jack H. ; Vanmechelen, Eugeen ; Zetterberg, Henrik ; Fagan, Anne M. ; Blennow, Kaj ; Bjerke, Maria ; Teunissen, Charlotte E. / Neurogranin as cerebrospinal fluid biomarker for Alzheimer disease : An assay comparison study. In: Clinical Chemistry. 2018 ; Vol. 64, No. 6. pp. 927-937.
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title = "Neurogranin as cerebrospinal fluid biomarker for Alzheimer disease: An assay comparison study",
abstract = "BACKGROUND: Neurogranin in cerebrospinal fluid (CSF) correlates with cognitive decline and is a potential novel biomarker for Alzheimer disease (AD) dementia. We investigated the analytical and diagnostic performance of 3 commonly used neurogranin assays in the same cohort of patients to improve the interpretability of CSF neurogranin test results. METHODS: The neurogranin Erenna{\circledR} assay from Washington University, St. Louis, MO (WashU); ELISA from ADx Neurosciences; and ELISA from Gothenburg University, M{\"o}lndal, Sweden (UGot), were compared using silver staining and Western blot after gel electrophoresis. Clinical performance of the 3 assays was compared in samples from individuals diagnosed with subjective cognitive decline (n 22), and in patients with AD (n 22), frontotemporal dementia (n 22), dementia with Lewy bodies (n 22), or vascular dementia (n 20), adjusted for sex and age. RESULTS: The assays detected different epitopes of neurogranin: the WashU assay detected the N-terminal part of neurogranin (S10-D23) and a C-terminal part (G49-G60), the ADx assay detected C-terminal neurogranin truncated at P75, and the UGot assay detected the C-terminal neurogranin with intact ending (D78). Spearman was 0.95 between ADx and WashU, 0.87 between UGot and WashU, and 0.81 between UGot and ADx. ANCOVA (analysis of covariance) showed group differences for ranked neurogranin concentrations in each assay (all P 0.05), with specific increases in AD. CONCLUSIONS: Although the 3 assays target different epitopes on neurogranin and have different calibrators, the high correlations and the similar group differences suggest that the different forms of neurogranin in CSF carry similar diagnostic information, at least in the context of neurodegenerative diseases.",
author = "Willemse, {Eline A.J.} and {De Vos}, Ann and Herries, {Elizabeth M.} and Ulf Andreasson and Sebastiaan Engelborghs and {Van Der Flier}, {Wiesje M.} and Philip Scheltens and Dan Crimmins and Ladenson, {Jack H.} and Eugeen Vanmechelen and Henrik Zetterberg and Fagan, {Anne M.} and Kaj Blennow and Maria Bjerke and Teunissen, {Charlotte E.}",
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Willemse, EAJ, De Vos, A, Herries, EM, Andreasson, U, Engelborghs, S, Van Der Flier, WM, Scheltens, P, Crimmins, D, Ladenson, JH, Vanmechelen, E, Zetterberg, H, Fagan, AM, Blennow, K, Bjerke, M & Teunissen, CE 2018, 'Neurogranin as cerebrospinal fluid biomarker for Alzheimer disease: An assay comparison study' Clinical Chemistry, vol. 64, no. 6, pp. 927-937. https://doi.org/10.1373/clinchem.2017.283028

Neurogranin as cerebrospinal fluid biomarker for Alzheimer disease : An assay comparison study. / Willemse, Eline A.J.; De Vos, Ann; Herries, Elizabeth M.; Andreasson, Ulf; Engelborghs, Sebastiaan; Van Der Flier, Wiesje M.; Scheltens, Philip; Crimmins, Dan; Ladenson, Jack H.; Vanmechelen, Eugeen; Zetterberg, Henrik; Fagan, Anne M.; Blennow, Kaj; Bjerke, Maria; Teunissen, Charlotte E.

In: Clinical Chemistry, Vol. 64, No. 6, 01.06.2018, p. 927-937.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Neurogranin as cerebrospinal fluid biomarker for Alzheimer disease

T2 - An assay comparison study

AU - Willemse, Eline A.J.

AU - De Vos, Ann

AU - Herries, Elizabeth M.

AU - Andreasson, Ulf

AU - Engelborghs, Sebastiaan

AU - Van Der Flier, Wiesje M.

AU - Scheltens, Philip

AU - Crimmins, Dan

AU - Ladenson, Jack H.

AU - Vanmechelen, Eugeen

AU - Zetterberg, Henrik

AU - Fagan, Anne M.

AU - Blennow, Kaj

AU - Bjerke, Maria

AU - Teunissen, Charlotte E.

PY - 2018/6/1

Y1 - 2018/6/1

N2 - BACKGROUND: Neurogranin in cerebrospinal fluid (CSF) correlates with cognitive decline and is a potential novel biomarker for Alzheimer disease (AD) dementia. We investigated the analytical and diagnostic performance of 3 commonly used neurogranin assays in the same cohort of patients to improve the interpretability of CSF neurogranin test results. METHODS: The neurogranin Erenna® assay from Washington University, St. Louis, MO (WashU); ELISA from ADx Neurosciences; and ELISA from Gothenburg University, Mölndal, Sweden (UGot), were compared using silver staining and Western blot after gel electrophoresis. Clinical performance of the 3 assays was compared in samples from individuals diagnosed with subjective cognitive decline (n 22), and in patients with AD (n 22), frontotemporal dementia (n 22), dementia with Lewy bodies (n 22), or vascular dementia (n 20), adjusted for sex and age. RESULTS: The assays detected different epitopes of neurogranin: the WashU assay detected the N-terminal part of neurogranin (S10-D23) and a C-terminal part (G49-G60), the ADx assay detected C-terminal neurogranin truncated at P75, and the UGot assay detected the C-terminal neurogranin with intact ending (D78). Spearman was 0.95 between ADx and WashU, 0.87 between UGot and WashU, and 0.81 between UGot and ADx. ANCOVA (analysis of covariance) showed group differences for ranked neurogranin concentrations in each assay (all P 0.05), with specific increases in AD. CONCLUSIONS: Although the 3 assays target different epitopes on neurogranin and have different calibrators, the high correlations and the similar group differences suggest that the different forms of neurogranin in CSF carry similar diagnostic information, at least in the context of neurodegenerative diseases.

AB - BACKGROUND: Neurogranin in cerebrospinal fluid (CSF) correlates with cognitive decline and is a potential novel biomarker for Alzheimer disease (AD) dementia. We investigated the analytical and diagnostic performance of 3 commonly used neurogranin assays in the same cohort of patients to improve the interpretability of CSF neurogranin test results. METHODS: The neurogranin Erenna® assay from Washington University, St. Louis, MO (WashU); ELISA from ADx Neurosciences; and ELISA from Gothenburg University, Mölndal, Sweden (UGot), were compared using silver staining and Western blot after gel electrophoresis. Clinical performance of the 3 assays was compared in samples from individuals diagnosed with subjective cognitive decline (n 22), and in patients with AD (n 22), frontotemporal dementia (n 22), dementia with Lewy bodies (n 22), or vascular dementia (n 20), adjusted for sex and age. RESULTS: The assays detected different epitopes of neurogranin: the WashU assay detected the N-terminal part of neurogranin (S10-D23) and a C-terminal part (G49-G60), the ADx assay detected C-terminal neurogranin truncated at P75, and the UGot assay detected the C-terminal neurogranin with intact ending (D78). Spearman was 0.95 between ADx and WashU, 0.87 between UGot and WashU, and 0.81 between UGot and ADx. ANCOVA (analysis of covariance) showed group differences for ranked neurogranin concentrations in each assay (all P 0.05), with specific increases in AD. CONCLUSIONS: Although the 3 assays target different epitopes on neurogranin and have different calibrators, the high correlations and the similar group differences suggest that the different forms of neurogranin in CSF carry similar diagnostic information, at least in the context of neurodegenerative diseases.

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U2 - 10.1373/clinchem.2017.283028

DO - 10.1373/clinchem.2017.283028

M3 - Article

VL - 64

SP - 927

EP - 937

JO - the Journal of Applied Laboratory Medicine

JF - the Journal of Applied Laboratory Medicine

SN - 0009-9147

IS - 6

ER -